Mothers who do not breastfeed their infants and those who wean early are at increased risk of cardiovascular disease (CVD) compared with mothers who practice exclusive or prolonged lactation. Mechanisms underlying this association remain to be determined. The long-term goal of this research is to identify biological mechanisms through which lactation reduces cardiovascular risk, thereby revealing targets for early intervention. The objective of this application is to determine the effect of lactation on vascular endothelial dysfunction, which is an early causal factor in the pathogenesis of atherogenic and hypertensive disease. The transition from pregnancy to early postpartum is characterized by marked increase in potent contributors to endothelial damage, including increased systemic and local inflammatory mediators, circulating lipids and visceral fat. The postpartum period, like the perimenopause, may therefore be a critical period of enhanced risk for inflammatory damage to vascular endothelium. The central hypothesis is that lactation reduces cardiovascular risk through its salutary effects on endothelial function during the critica 1st year postpartum. This hypothesis is based on preliminary data collected in the applicant's laboratory and is further supported by published literature. The rationale for the proposed research is that determining mechanisms through which lactation reduces endothelial dysfunction will identify new therapeutic targets for reduction of CVD risk among parous women. This hypothesis will be tested using three specific aims: 1) Determine the effect of lactation on endothelial function, indexed by brachial artery flow-mediated dilation (FMD) assessed at 2, 6 and 12 months postpartum; 2) Quantify the effect of lactation on systemic and vascular inflammatory mediators that contribute to endothelial dysfunction; 3) Measure the effect of lactation on metabolic risk factors that impair endothelial function. These aims will be achieved through a longitudinal study of 120 primiparous women recruited in the third trimester of pregnancy, with oversampling of low SES, overweight, and African-American women, who are at increased risk for future CVD. Infant feeding intention will be assessed at 3rd trimester. Pro-inflammatory and metabolic biomarkers will be assessed at 3rd trimester, and at 2, 6 and 12 months postpartum. Acute endothelial effects of breast- or bottle-feeding will be measured by FMD assessed before and after infant feeding at 2 months postpartum. FMD % change during the first year will be used to test the cumulative effects of feeding method and lactation characteristics (duration, intensity, lactation hormones) on endothelial function. The approach is innovative because no studies to date have examined effects of lactation on endothelial function, inflammation and metabolism during the first postpartum year, when vascular endothelium may be most susceptible to injury, and when acute effects of lactation may be observed. The proposed research is significant because it is expected to advance understanding of early mechanisms of CVD, the #1 cause of death for women in the U.S, and has potential for widespread positive impact on women's health.